Kaposi's sarcoma-associated herpesvirus (KSHV) is consistently identified in Kaposi's sarcoma and body cavity-based lymphoma KSHV encodes a transforming protein called K1 which is structurally similar to lymphocyte receptors We have found that a highly conserved region of the cytoplasmic domain of K1 resembles the sequence of immunoreceptor tyrosine-based activation motifs (ITAMs) To demonstrate the signal-transducing activity of K1, we constructed a chimeric protein in which the cytoplasmic tail of the human CD8` polypeptide was replaced with that of KSHV K1 Expression of the CD8-K1 chimera in B cells induced cellular tyrosine phosphorylation and intracellular calcium mobilization upon stimulation with an anti-CD8 antibody Mutational analyses showed that the putative ITAM of K1 was required for its signal-transducing activity Furthermore, tyrosine residues of the putative ITAM of K1 were phosphorylated upon stimulation, and this allowed subsequent binding of SH2 -containing proteins These results demonstrate that the KSHV transforming protein K1 contains a functional ITAM in its cytoplasmic domain and that it can transduce signals to induce cellular activation PUBLICATIONS Lee, H, Guo, J, Li, M , Choi, J-K, DeMaria, M, Rosenzweig, M, and Jung, JU Identification of an immunoreceptor tyrosine-based activation motif of K1 transforming protein of Kaposi's sarcoma-associated herpesvirus Mol Cell Biol 1998; 18, 5219-5228